Mechanisms of proteinuria in human glomerulonephritis.

Mechanisms of proteinuria in human glomerulonephritis.
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人肾小球肾炎蛋白尿的机制。

DOI:
10.1172/jci110669
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发表时间:
1982
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Deen,WM
Deen,WM
中科院分区:
--
文献类型:
--
作者:
Myers,BD;Okarma,TB;Friedman,S;Bridges,C;Ross,J;Asseff,S;Deen,WM

文献摘要

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我们评估了28例肾小球肾炎患者的肾小球屏障功能。分级大小的中性右旋糖酐被用来表征屏障的尺寸选择特性。电荷选择性是通过电聚焦尿蛋白来表征的。IgG清除率分数(相对于可自由渗透菊粉)、小于或大于100 × 10(-5)分别用于区分轻度(组I, n = 13)和重度(组II, n = 15)尿IgG渗漏。较小的右旋糖酐(半径20-50 A)的清除率相似,但较大的右旋糖酐(半径52-60 A)的清除率在II组患者中相对于I组患者有所升高。通过双峰孔径分布的溶质运输模型显示,I组和II组患者的低模式孔径半径值约为51- 55a。相比之下,II组的上模孔半径比I组大得多,分别约为87-97 A和72-77 A。1组患者尿蛋白电聚焦显示以白蛋白为主(等电点5.2)。然而,在II组患者中,免疫球蛋白排泄丰富。此外,IgG2和IgG4尿液和血浆洗脱液中阴离子、中性和阳离子(等电点5.5-8.5)的分布相似。我们的结论是,当肾小球肾炎与选择性蛋白尿相关时,如在第一组中,相对较小的阴离子蛋白的静电延迟被孤立地减少。然而,尿IgG渗漏(II组)主要是由于肾小球膜上的一个扩大的孔亚群的发育,这些孔对大尺寸和不同电荷的蛋白质具有高度渗透性。图片
We evaluated glomerular barrier function in 28 patients with glomerulonephritis. Neutral dextrans of graded size were used to characterize the size-selective properties of the barrier. Charge selectivity was characterized by electrofocusing excreted urinary proteins. A fractional IgG clearance (relative to freely permeable inulin), smaller or greater than 100 x 10(-5) was used to distinguish patients with minor (group I, n = 13) and major (group II, n = 15) urinary IgG leakage, respectively. Fractional clearances of smaller dextrans (radii 20-50 A) were similar, but those of larger dextrans (radii 52-60 A) were elevated in group II relative to group I patients. A model of solute transport through a bimodal pore size distribution revealed the values for pore radius in the lower mode to approximate 51-55 A in both group I and group II patients. Pore radius in the upper mode, by contrast, was much larger in group II than in group I patients, approximating 87-97 vs. 72-77 A, respectively. Electrofocusing of urinary protein from group I patients revealed mostly albumin (isoelectric point 5.2). In group II patients, however, immunoglobulin excretion was copious. Moreover, the distribution of anionic, neutral, and cationic species (isoelectric points 5.5-8.5) in urinary and plasma eluates of IgG2 and IgG4 was similar. We conclude that when glomerulonephritis is associated with selective albuminuria, as in group I,, there is an isolated reduction of electrostatic retardation of relatively small anionic proteins. Major urinary IgG leakage (group II), however, appears to result from the development in the glomerular membrane of a subpopulation of enlarged pores that are highly permeable towards proteins of large size and varying charge.Images